The anti-inflammatory potential of quercetin and L-2-oxothiazolidine-4-carboxylate (OTC) in developing scar tissue

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Abstract

Loss of physiological function, uncomfortable symptoms and various disease processes are thought to be directly related to the formation of scar tissue following tissue damage. Between ten and thirty percent of patients requiring spinal surgery suffer from failed back surgery syndrome. The pain and instability resulting from failed back syndrome often requires medical treatment and may even require additional surgeries to alleviate its associated symptoms. Following surgery, scar tissue forms that often becomes adherent to the dura and entangled in the ganglia and nerve fibers of the spinal nerves. This scar tissue is considered to play a major role in the development of failed back syndrome.
Following tissue injury, excessive oxidative stress and inflammation are considered to be the primary stimulators behind increased fibroblast proliferation and activation, resulting in abundant extracellular matrix deposition. The excessive laying down of extracellular matrix ultimately leads to abundant scar tissue formation. I hypothesized that reducing oxidative stress and inflammation will mitigate scar tissue formation and produce a better outcome after spinal surgeries. Quercetin is a dietary flavonoid with anti-oxidant and anti-inflammatory properties that has been shown to improve the outcome following injury to the spinal cord and reduce the proliferation of fibroblasts. L-2-Oxothiazolidine-4-carboxylate (OTC) also minimizes inflammation and protects against oxidative stress by promoting the synthesis of the potent antioxidant and anti-inflammatory agent glutathione. OTC reduces airway inflammation in asthma models and is potentially capable of modulating extracellular matrix production. Treatment with these two agents was hypothesized to decrease oxidative stress and inflammation, thereby causing an amelioration of scar tissue formation following spinal surgery and improve the outcome. Morphological changes observed initially indicated that improvements in wound healing were occurring in the experimentally treated tissues. In addition, the scar tissue area and the lateral widths of the peridural scar forming between the muscular tissue areas suggested a reduction in the scar size. Although inflammatory cell numbers increased slightly in the experimental treatment groups, particularly during the initial three day post laminectomy time point, this increase was not statistically significant. While quercetin and OTC did not appear to inhibit the influx of inflammatory cells following laminectomy, they did appear to induce a more beneficial wound healing environment. It is possible that these agents are affecting parameters of wound healing not considered by these studies. For instance the myriad of processes mediated by growth factors and cytokines involved in wound healing process may play a much greater role than the inflammatory cells themselves. In conclusion, reducing oxidative stress and inflammation by these agents to ameliorate scar tissue formation following spinal laminectomy was supported by the observed morphology, but not supported by the quantification of inflammatory cells. Additional studies investigating the efficacy of quercetin and OTC on the wound healing process are needed to further understand the role they play in repair and scar tissue formation.